Choice Of Adjuvant Therapy Research Articles

The prognostic values of lymph node ratio for gynecological cancer: a systematic review and meta-analysis.

The aim of this study was to determine the relationship between the lymph node ratio (LNR) and the prognostic values of gynecological cancer. PubMed, Web of Science, Embase, and the Central Cochrane Library were used to search for studies on LNR and gynecological cancer published before 18 April 2024. The effect measure for meta-analysis of primary outcomes was the hazard ratio (HR) for overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Pooled HRs and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Sensitivity analysis was applied to evaluate the robustness of the results. The I 2 statistic was used to measure heterogeneity. Subgroup analysis and meta-regression were chosen to illustrate the potential heterogeneity of the risk factors for outcomes. Publication bias was assessed using Egger's test and Begg's funnel plots. A total of 34 studies with 23,202 cases were included in this meta-analysis. A meta-analysis found that higher LNR was associated with worse OS (HR = 2.42, 95% CI: 2.07-2.83; I 2 = 77.4%, p < 0.05), PFS (HR = 1.97, 95% CI: 1.66-2.32; I 2 = 0.00%, p > 0.05), and DFS (HR = 3.18, 95% CI: 2.12-4.76; I 2 = 64.3%, p < 0.05). Moreover, meta-analysis revealed significant differences in the association between LNR and OS of cervical cancer (CC) (HR = 2.53, 95% CI: 1.94-3.31; I 2 = 72.6%, p < 0.05), ovarian cancer (OC) (HR = 2.05, 95% CI: 1.66-2.54; I 2 = 76.7%, p < 0.05), endometrial cancer (EC) (HR = 2.16, 95% CI: 1.48-3.16; I 2 = 53.6%, p < 0.05), and vulvar cancer (VC) (HR = 8.13, 95% CI: 3.41-19.43; I 2 = 57.2%, p < 0.05). We observed a clear association between higher LNR and poorer prognosis in our study of patients with gynecological cancer. Further prospective studies are warranted to determine the optimal LNR and whether LNR can guide adjuvant therapy use in gynecological cancer. It is essential to conduct further prospective studies to establish the optimal LNR threshold, determine the minimum threshold of lymph node removal, and investigate whether LNR can serve as a reliable marker for guiding adjuvant therapy choices in gynecological cancer. https://www.crd.york.ac.uk/PROSPERO/#recordDetails, CRD42024541187.

Lnsights into Adjuvant Systemic Treatment Selection for Patients with Stage III Melanoma: Data from the Dutch Cancer Registry.

Patient demographics and shared decision making might influence the choice of adjuvant therapy for stage III melanoma. To identify factors for treatment selection of patients diagnosed with stage III melanoma to better understand current treatment decisions and improve further treatment counseling. Data from 2007 patients diagnosed with stage III melanoma, between December 2018 and 2021, sourced from the Dutch Cancer Registry, were analyzed. Among the cohort, 48.7% received no therapy, 45.8% received checkpoint inhibition, and 5.5% received targeted therapy (TT). Patients foregoing therapy were significantly older [67.0 years (range 53.0-77.0) vs. 62.0 year (range 52.0-72.0)], had poorer performance scores (PS), and higher Charlson Comorbidity Index scores compared to those receiving therapy (p<0.001). Patients undergoing therapy had significantly higher median Breslow thickness (3.3mm vs. 2.2mm) and higher prevalence of ulceration (49.9% vs. 38.1%). Those with connective tissue disease and/or congestive heart disease were more likely to receive TT [odds ration (OR) 8.1; 95% confidence interval (CI) 1.7-37.6 and OR 9.3; 95% CI 1.2-72.2, respectively]. Median treatment time among strata for disease recurrence was 4.26months (3.69-4.82) for immunotherapy and 3.1months (0.85-5.36) for TT (p=0.298). Patients who developed recurrent disease were equal across treatment types (p=0.656). The number of patients with grade 3 complications was different for each treatment type [immunotherapy: 17.8% vs. TT: 37.3% (p<0.001)]. Age, PS, and Breslow thickness seem to influence adjuvant treatment decisions. Clinicians' preference for immunotherapy might play a role in counseling BRAF-positive patients for adjuvant therapy, this however, cannot be confirmed in this dataset. Overall, only a small proportion of patients completed adjuvant treatment.

Real-world duration of interruptions in imaging and endocrine therapy (ET) after pregnancy in early-stage estrogen receptor (ER) positive breast cancer (BC).

11157 Background: Pre-menopausal women with early-stage ER-positive BC often desire the option for future fertility. The POSITIVE trial demonstrated that a pause in ET to conceive is safe. However, the real-world durations of these pauses, as well as how many patients resume ET, are unclear. Additionally, there are limited data about when and if women reestablish imaging surveillance after childbirth. Methods: We generated a cohort of BC patients with a pregnancy-related ICD diagnosis from the Oncoshare registry. This registry merges EMR and California Cancer Registry data for patients treated in the Stanford Health Care Alliance which includes an academic hospital, a community hospital, and a community practice network. Included patients had ≥1 pregnancy after a diagnosis of stage 0-3 ER-positive BC. Chart review confirmed pregnancy and was used to abstract treatment information. Data are presented as unadjusted percentages or medians with interquartile ranges (IQR). Among patients without bilateral mastectomies, we compared time from delivery to first imaging (MRI or mammogram) for those who breastfed vs not and those who restarted ET vs not using the Wilcoxon rank sum test. Results: Of the 317 charts reviewed, 71 were included. Most exclusions were due to no pregnancy (46%) or ER-negative disease (25%). Year of diagnosis ranged from 1994 to 2020, with the majority (79%) from 2010 to 2020. Median age at diagnosis was 33 years (IQR 30-35). The distribution of stages was 18% in situ disease, 51% stage 1, 17% stage 2, 14% stage 3. 23% (16/71) of women never started ET, with 14 attributing this decision to desiring pregnancy. Among the 55 women who started ET, 75% received tamoxifen without ovarian suppression (OS). After 2015, use of OS became more prevalent (45% of ET), coinciding with the emergence of the SOFT/TEXT data. The median time from ET onset to a pause for pregnancy was 32 months (IQR 22-53), and the median ET pause to delivery was 23 months (IQR 14-48). We recorded 90 pregnancies resulting in 85 live births. After delivery of their first child, the median follow-up was 3.8 years (IQR 2.0-6.8). 40% of patients never restarted ET. Those who did restart did so at a median of 5 months (IQR 3-11) post-delivery. Imaging surveillance resumed for 42% (27/64) at a median of 6 months post-delivery [IQR 3-11]. Time from delivery to imaging was similar between those who restarted ET and those who did not (p=0.91), and between those who breastfeed and those who did not (p=0.42). Conclusions: These data support prior work showing that fertility concerns strongly influence adjuvant therapy choice in ER-positive BC. The ET resumption rate after pregnancy was lower in our analysis compared to the POSITIVE trial (73% vs. 40%). Only 42% of women resumed surveillance imaging. This points to clear gaps between the clinical trial population and the real-world clinical setting.

Choice of adjuvant therapy for HER2-positive breast cancer in real clinical practice: analysis of physician preferences in the Russian Federation

Adjuvant therapy with trastuzumab made a significant contribution to improving disease-free and overall survival rates in patients with HER2-positive breast cancer. However, in a number of clinical situations the risk of disease recurrence remains increased. Carrying out neoadjuvant treatment followed by post-neoadjuvant therapy, depending on the degree of pathomorphological response, is the modern standard, allowing to cure a significantly larger number of patients. This became possible thanks to the expansion of the arsenal of terget anti-Her drugs and the introduction into real clinical practice of double anti-HER2 blockade (trastuzumab + pertuzumab) and an antibody conjugate with a cytostatic drug – trastuzumab emtansine. To assess actual clinical practice in the Russian Federation, a survey study “Therapy of HER2-positive breast cancer” was conducted. The survey involved 50 specialists from different regions of the country who are directly involved in developing a treatment plan for patients, which allows them to reflect the preferences of leading chemotherapists regarding tactics for HER2-positive breast cancer. This publication reflects the results of part of the survey, devoted to the choice of adjuvant and post-neoadjuvant therapy for HER2-positive breast cancer. Identified a clear positive trend in favor of neoadjuvant treatment followed by post-neoadjuvant therapy using modern targeted drugs such as pertuzumab and trastuzumab emtansine. The survey results show that 68% of patients with RCB-II–III residual tumor receive post-neoadjuvant trastuzumab emtanzine, in 2021 this figure was only 24%. The absolute majority of patients who have not received neoadjuvant therapy, but have N2–3 stage, receive double anti-HER2 therapy with trastuzumab + pertuzumab in the adjuvant setting. High adherence to the therapy was noted, as 97% of patients complete the planned course of T-DM1, and 91.2% of patients complete a year of adjuvant anti-HER2 therapy. These figures are noticeably higher than the indicators of registration studies. Issues of effectiveness come to the fore in choosing therapy. Issues of drug availability remain relevant, but are not decisive. The survey also revealed factors that were not obvious at first glance and influenced treatment results.

Adjuvant treatment and outcome of stage III melanoma patients: Results of a multicenter real-world German Dermatologic Cooperative Oncology Group (DeCOG) study

PurposeClinical trials demonstrated significantly improved recurrence-free survival (RFS) of melanoma patients receiving adjuvant treatment. As data from controlled trials are based on selected populations, we investigated adjuvantly treated stage III melanoma patients under real-world conditions. Patients and methodsIn a prior multicenter cohort study, stage III-IV melanoma patients were analysed for their choice of adjuvant therapy. In this follow-up study, we examined RFS, overall and melanoma-specific survival (MSS) and response to the subsequent treatment of 589 stage III patients (232 BRAF-mutated) receiving adjuvant PD-1 inhibitors (PD1; n = 479) or targeted therapy (TT; n = 110). ResultsThe median follow-up of the total cohort was 25.7 months. The main reason for premature discontinuation of adjuvant therapy was disease progression in PD1- (28.8%, n = 138/479) and adverse events in TT-treated patients (28.2%, n = 31/110).Among BRAF-mutated patients, RFS at 24 months was 49% (95% CI 40.6–59.0%) for PD1- and 67% (95% CI 58–77%) for TT-treated patients. The risk of recurrence was higher for BRAF-mutated PD1 than TT (hazard ratio 1.99; 95% CI 1.34–2.96; hazard ratio adjusted for age, sex and tumour stage, 2.21; 95% CI 1.48–3.30). Twenty-four months MSS was 87% (95% CI 81.0–94.1) for PD1 and 92% (95% CI 86.6–97.0) for TT.Response to subsequent systemic treatment for unresectable disease was 22% for all PD1- and 16% for TT-treated patients. ConclusionsPD1-treated patients had more and earlier recurrences than TT patients. In BRAF-mutated patients, adjuvant TT might prevent early recurrences more effectively than PD1 treatment. Management of recurrence despite adjuvant treatment is challenging, with low response to current therapeutic options.

The Role of the Surgeon in the Germline Testing of the Newly Diagnosed Breast Cancer Patient

For patients with newly diagnosed breast cancer, information regarding hereditary predisposition can influence treatment decisions. From a surgical standpoint, patients with known germline mutations may alter decisions of local therapy to reduce the risk of second breast primaries. This information may also be considered in the choice of adjuvant therapies or eligibility for clinical trials. In recent years, the criteria for the consideration of germline testing in patients with breast cancer has expanded. Additionally, studies have shown a similar prevalence of pathogenic mutations in those patients outside of these traditional criteria, prompting calls for genetic testing for all patients with a history of breast cancer. While data confirms the benefit of counseling by certified genetics professionals, the capacity of genetic counselors may no longer meet the needs of these growing numbers of patients. National societies assert that counseling and testing can be performed by providers with training and experience in genetics. Breast surgeons are well positioned to offer this service, as they receive formal genetics training during their fellowship, manage these patients daily in their practices, and are often the first providers to see patients after their cancer diagnosis.

Comparative analysis of adjuvant therapy for stage III BRAF-mut melanoma: A real-world retrospective study from single center in China.

BRAF V600 mutation is the most common oncogenic alternation in melanoma and is visible in around 50% of cutaneous and 10%-15% of acral or mucosal subtypes. Currently, immunotherapy with anti-PD-1 blockade and dual-targeted therapy with Dabrafenib plus trametinib (D + T) target therapy have been approved as adjuvant therapies for Stage III melanoma with BRAF V600 mutation. According to their phase III clinical trials, 3-year recurrence-free survival (RFS) is around 60% for both types of treatment. However, early disease control was slightly more effective with targeted therapy than immunotherapy. With different drug approval deadlines in China, anti-PD1 monotherapy, D + T combination, and Vemurafenib (V) monotherapy have all been used in real clinical practice as adjuvant settings for stage III BRAF-mut melanoma in recent years. We conducted this retrospective study to evaluate the efficacy of different treatments in the Chinese melanoma population. Patients who underwent radical surgery and were diagnosed as Stage III melanoma harboring BRAF V600 mutation by pathological report were retrospectively identified at Fudan University Shanghai Cancer Center from January 2017 to December 2021. Patients with mucosal melanoma, or with follow-up of <6 months, or receiving other adjuvant treatment were excluded. Pearson's chi-squared test or Fisher's exact test was performed for univariable analysis of the different adjuvant groups. Log-rank analysis was used to identify prognostic factors for relapse-free survival (RFS). Ninety-three patients with resected stage III melanoma with BRAF V600E mutation were identified in our study, including 25 patients receiving adjuvant anti-PD-1 immunotherapy (PD-1), 25 receiving adjuvant D + T, 23 receiving V, and 20 patients with observation-only (OBS). There were no statistical differences between treatment groups in baseline characteristics including age, gender, subtypes, primary thickness, ulceration, and nodal involvement. Median relapse-free survival (RFS) time was not reached in the D + T group, 15 months in the V group, 15 months in the PD-1 group, and 10 months in the OBS group, respectively. Compared to OBS, all three other groups showed a tendency to benefit from RFS, while only D + T achieved a statistical difference (p = 0.002). However, compared to D + T, anti-PD-1 monotherapy also showed significantly worse relapse control (p = 0.032). For Chinese stage III melanoma with BRAF mutation, both novel targeted therapy and immunotherapy showed potential benefits in relapse-free survival compared to observation only. Dual-targeted D + T therapy may still be the best choice for adjuvant therapy because anti-PD-1 monotherapy has failed to report equivalent efficacy in real-world practice.

Uniform Noting for International application of the Tumor-stroma ratio as Easy Diagnostic tool: The UNITED study - An update

Background: The UNITED study researches the tumor-stroma ratio (TSR) as prognostic parameter in colon cancer. A high amount of stroma has retrospectively been proven to lead to a worse overall and disease-free survival (OS and DFS, respectively), potentially influencing the choice for adjuvant therapy. The Union for International Cancer Control (UICC) and College of American Pathologists (CAP) supported the importance of this parameter, but indicated the necessity of a prospective international multicenter trial using a quality program for scoring. Hence, this study prepares the TSR for implementation in current routine pathology diagnostics in addition to the TNM classification.

Emerging trends in the prediction of pathological tumour response in rectal cancer following neoadjuvant therapy.

The treatment landscape of locally advanced rectal cancer (LARC) is moving towards total neoadjuvant therapy and potential organ preservation. Multimodality neoadjuvant therapy (NAT) and surgery remain the standard-of-care for LARC, with consideration for adjuvant chemotherapy. Neoadjuvant chemotherapy alone is another emerging strategy.1 Due to variation in multimodality treatment choice, biomarkers to predict response to NAT could personalize treatment plans for patients.2 Of particular interest are predictors of pathologic complete response (pCR) to guide selection for a watch and wait approach, or identify those who would benefit from surgery due to poor response to NAT or a higher risk of disease relapse. Tumour response to NAT is a complex interplay between variables including tumour biology, patient factors, and the sequencing and timing of the selected NAT approach. Presently available modalities (MRI and endoscopy) can aid assessment but do not predict for tumour response. There are currently no clinically actionable biomarkers to predict NAT response, however several promising contenders are emerging.2 Circulating tumour DNA (ctDNA) has been shown as a risk-stratification tool to guide adjuvant therapy choice in patients following colon cancer resection.3 The presence of ctDNA following long course chemoradiation and surgery is an adverse prognostic factor.4 Evidence for ctDNA in the neoadjuvant setting for LARC is also evolving. As a marker for minimal residual disease, studies have demonstrated that detectable ctDNA predicts for poorer response to NAT and potentially identifies patients that should proceed to surgery rather than a watch and wait strategy.5, 6 Other biochemical markers such as microRNA and tumour-infiltrating lymphocytes are also being evaluated.7, 8 The gut microbiome has a role in the carcinogenesis of colorectal cancer, and potentially predicts response to anticancer therapy through the effect of certain bacteria on pharmacokinetics, pharmacodynamics and immune response.9 However, questions remain regarding the specific microbiome biomarkers that can predict LARC response to NAT and its utility in clinical practice is currently limited.9 Immunogenomics is becoming increasingly relevant to the management of LARC, with immune checkpoint inhibitors exhibiting high response rates in mismatch repair deficient (dMMR) tumours and 100% clinical complete response in dMMR LARC.10 Initiatives such as the Cancer Genome Atlas Program are genomically sequencing colorectal cancers to identify genomic alterations beyond microsatellite instability that may predict responsiveness to immunotherapy and the likelihood of a pCR.11 Radiomics is a process whereby disease features, or ‘radiological biomarkers’ are extracted from standard patient imaging, constructing an algorithm which can then aid in predicting treatment response.12 T2 weighted MRI-based software for LARC successfully predicts pCR and nodal status post-NAT.13 Combined radiomics with both multi-parameter MRI (T1/T2/Contrast enhanced) and functional PET-CT may provide better predictive value for pCR.14 Currently, the widespread adoption of radiomics has been hindered by the technological and cost burden, limited reproducibility of data, and time-intensive manual data extraction.13 Larger prospective trials are required to validate its use in LARC management.13, 15 With the adoption of Artificial Intelligence (AI) and deep learning, data extraction will become increasingly accessible and construct reproducible algorithms,13 making clinical application feasible. Body composition measurement based on standard CT-staging is another ‘radiological biomarker’.16 Body composition is more accurate than body surface area for systemic therapy dosing, and predicting poor tolerance to chemotherapy in colorectal cancer.17 Recent evidence has suggested that skeletal muscle area pre-NAT can predict tumour response and survival outcomes for LARC, presenting a promising area for future studies.16 In summary, multiple promising biomarkers are emerging to identify the optimal individualized treatment paradigm for patients with LARC. It is hoped that further research and increasing validation of new technologies such as AI, will tailor future personalized decision making for patients with LARC. Open access publishing facilitated by The University of Melbourne, as part of the Wiley - The University of Melbourne agreement via the Council of Australian University Librarians. Matthew Y. Wei: Writing – original draft; writing – review and editing. Yasser Arafat: Validation; writing – review and editing. Margaret Lee: Validation; writing – review and editing. Suzanne Kosmider: Validation; writing – review and editing. Matthew Loft: Validation; writing – review and editing. Ian Faragher: Validation; writing – review and editing. Peter Gibbs: Conceptualization; validation; writing – review and editing. Justin Yeung: Conceptualization; supervision; writing – review and editing.

Residual cancer is a strong predictor of survival in T3 incidental gallbladder cancer

Background and purposeIndex cholecystectomy is insufficient for curing T3 incidental gallbladder cancer (IGC), and once residual cancer (RC) is found, the prognosis is often poor. The purpose of this study was to investigate the effect of RC on the prognosis and the optimal choice of adjuvant therapy for R0 reresection patients with T3 IGC.MethodsWe retrospectively reviewed data from patients with T3 IGC who underwent radical reresection from January 2013 to December 2018. RC was defined as histologically proven cancer at reresection. Demographics and tumour treatment-related variables were analysed in correlation with RC and survival. Adjuvant (Adj) chemoradiotherapy (CRT) was correlated with overall survival (OS) and disease-free survival (DFS).ResultsOf the 167 patients with IGC who underwent surgery, 102 underwent radical extended resection. Thirty-two (31.4%) RCs were found. Hepatic side tumours (T3h) and both side tumours (T3h + T3p) were associated with the presence of RC. In multivariate analysis, RC and lymph node metastasis were independent prognostic factors for DFS and OS (P < 0.05). RC was associated with a significantly shorter median OS (20 vs. 53 months; P < 0.01) and DFS (11 vs. 40 months; P < 0.001) despite R0 resection. For R0 reresection patients with RC and/or lymph node metastasis, Adj CRT significantly improved OS (P = 0.024).ConclusionResidual cancer and lymphatic metastasis are important factors for the poor prognosis of T3 IGC despite R0 resection, and these patients should actively receive adjuvant therapy.

Allergic Fungal Rhinosinusitis: The Role and Expectations of Biologics

Allergic fungal rhinosinusitis (AFRS) is a noninvasive subtype of chronic rhinosinusitis with nasal polyps (CRSwNP) that usually develops in immunocompetent atopic individuals and is more common in geographic regions characterized by warm temperatures and high humidity, conducive to higher environmental fungal presence. Allergic fungal rhinosinusitis usually presents with unique computed tomography findings and significant polyp burden, yet patients often report minimal sinus symptoms. Patients with AFRS often have extremely elevated serum total and fungal-specific IgE levels. Treatment almost always requires surgery, in which adjuvant medical therapy is critical to success. However, until recently the choice of adjuvant therapy has consisted primarily of either oral and/or topical steroids. Although oral corticosteroids decrease recurrence after surgery, data for the effectiveness of other adjunctive pharmacologic agents, including topical and oral antifungal agents and immunotherapy, have remained unclear and hence are not recommended in recent guidelines including the International Consensus of Allergy and Rhinology. Three biologics, omalizumab, dupilumab, and mepolizumab, have recently been approved for treating CRSwNP in general, but clinical trials to date with these biologics did not involve AFRS patients. Recently published case reports and smaller prospective studies have shown good efficacy of these biologics on the AFRS subgroup of patients. This article provides an overview of the understanding of the pathophysiology of AFRS, implications of this understanding on the possible role of biologics, and clinical reports on the use of biologics in treating AFRS. Because biologics are indicated for treating CRSwNP, follow up real-world evidence studies are needed for AFRS.

Abstract 5114: Ultra-sensitive detection of minimal residual disease (MRD) through whole genome sequencing (WGS) using an AI-based error suppression model in resected early-stage non-small cell lung cancer (NSCLC)

Abstract Background: Early detection of recurrence and monitoring of MRD post-surgery is critical for clinical decision-making to tailor adjuvant therapy. In early-stage NSCLC, circulating tumor DNA (ctDNA) detection is especially challenging, requiring highly sensitive and specific assays. Therefore, we used a WGS approach (MRDetect) for ultra-sensitive ctDNA detection in NSCLC patients (pts) undergoing curative surgery. Methods: We conducted a pilot study to evaluate the MRDetect approach in serial plasma samples (including pre-surgery, post-surgery and follow-up [f/u] timepoints) from resected stage IB-IIIA NSCLC pts. Pts underwent routine surveillance by computed tomography scans. ctDNA was extracted from ~1mL plasma. MRDetect uses WGS by a tumor-informed approach (sequencing coverage 40x for tumor, 20x for plasma DNA) combined with AI-based error suppression models (trained and calibrated with a non-cancer cohort, n=17) to increase the signal to noise ratio for precise ctDNA detection, and improve the accuracy of readouts especially for low tumor burden scenarios. The assay reports the detection and quantification of ctDNA burden in blood with a prognostic value for risk of recurrence. The ability of the assay to predict recurrence from a single sample, taken at the clinical landmark point (median 1.6 mths post-surgery, range 0.1-6.5) was evaluated. Results: Overall, 52 NSCLC pts were enrolled (n=88 plasma samples) with median clinical f/u of 32.6 mths (range 3.1-98.6). There were 43 pts with post-surgery landmark samples, with median age 62 years, 70% were male, 79% were adenocarcinoma and 49% were EGFR mutated. 26% were stage IB and 37% each were stage II and III. There were 15/18 (sensitivity 83%) pts with confirmed radiological recurrence in which MRDetect was positive, including 6/7 (86%) EGFR mutated pts. The median RFS in MRDetect positive pts was 15.2 mths (range 3.7-33.4). Among 25 pts with no recurrence (median f/u 25.6 mths), MRDetect reported 4 pts to be MRD positive (specificity 84%). These results were consistent between EGFR mutated (sensitivity 86%, specificity 86%) and wildtype pts (sensitivity 82%, specificity 82%). For longitudinal samples (n=17 pts), negative ctDNA was associated with absence of recurrence in 14/15 pts (specificity 93%). At the AACR meeting, results from a planned larger validation study will be presented. Conclusion: Using a robust WGS implemented AI-based computational platform (MRDetect), we demonstrate high sensitivity and specificity detection of MRD in both EGFR mutated and wildtype NSCLC. With an increasing number of therapeutic options in the adjuvant setting for NSCLC, an ultra-sensitive MRD assay has the potential to facilitate personalized clinical decision-making for tailoring both the need and choice of adjuvant therapies. Citation Format: Aaron C. Tan, Stephanie P. Saw, Gillianne G. Lai, Kevin L. Chua, Angela Takano, Boon-Hean Ong, Tina P. Koh, Amit Jain, Wan Ling Tan, Quan Sing Ng, Ravindran Kanesvaran, Tanujaa Rajasekaran, Sunil Deochand, Dillon Maloney, Danielle Afterman, Tomer Lauterman, Noah Friedman, Imane Bourzgui, Nidhi Ramaraj, Zohar Donenhirsh, Ronel Veksler, Jonathan Rosenfeld, Ravi Kandasamy, Iman Tavassoly, Boris Oklander, Asaf Zviran, Wan-Teck Lim, Eng-Huat Tan, Anders J. Skanderup, Mei-Kim Ang, Daniel S. Tan. Ultra-sensitive detection of minimal residual disease (MRD) through whole genome sequencing (WGS) using an AI-based error suppression model in resected early-stage non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5114.

Real-world changes in the clinical management of resected stage III melanoma at high risk of local recurrence in the era of modern systemic therapies.

e21575 Background: Adjuvant systemic therapies (ST) for patients with resected stage III melanoma have improved relapse-free survival; however, the role of adjuvant radiotherapy (RT), previously the mainstay adjuvant treatment, is undefined in the modern ST era. Real-world data detailing clinical practice changes and its impact on outcomes are needed to help inform the choice of adjuvant therapy for patients with resected stage III melanoma. Methods: In this single-center retrospective study, patients from Princess Margaret Cancer Centre with resected stage III cutaneous melanoma treated between 2010 and 2019 and fitting the 2016 Cancer Care Ontario guidelines for adjuvant RT were included. Demographic, pathological, and clinical data were abstracted from electronic medical records. PFS was defined as the time from lymph node dissection to local-regional recurrence in the treated nodal basin or distant recurrence. OS was defined as time from lymph node dissection to death by any cause. The Log-rank method was applied to assess survival endpoints. A p-value &lt; 0.05 was considered statistically significant. Results: From 4,959 records reviewed, 109 patients were identified. Median age at time of surgical resection was 59.4 years (23.6-89.8), and 74 (68%) were male. Type of adjuvant therapy and number of local-regional recurrences (LR) are expressed in the table. The median follow-up among those alive at last follow-up was 54.2 months (range 1.9-122). The proportion of patients receiving adjuvant RT was higher between 2010 and 2014 than it was between 2015 and 2019 (59% to 26%), whilst the proportion of those receiving adjuvant ST progressively grew (3% to 50%). LR &gt; 90 days following lymph node dissection as the first site of relapse or synchronously with progression to metastatic disease was rare in patients treated with either adjuvant RT (6.8%) or adjuvant ST (14.3%, chi-square p = 0.33). Median progression free survival was 12.3 months in patients treated with adjuvant RT and 43.8 months in patients treated with adjuvant ST (p = 0.007). Overall survival was not significantly different (p = 0.08). Conclusions: The advent of ST has changed our institution’s clinical practice with ST replacing RT as the primary adjuvant treatment modality. Our data suggests that in the current adjuvant treatment landscape, omission of RT does not seem to increase rates of local-regional recurrences, and patients with resected stage III melanoma can be safely spared from adjuvant RT without detrimental effect on survival.[Table: see text]

Multicenter real-world data of adjuvant treatment and disease outcome of patients with melanoma with high-risk of recurrence.

9570 Background: Clinical trials demonstrated a significantly improved recurrence-free survival (RFS) of melanoma patients treated adjuvantly with immune checkpoint inhibition (ICI) and targeted therapy (TT). As data from controlled trials are based on selected populations, we investigated melanoma patients with high risk of recurrence who opted for ICI, TT, or no adjuvant treatment (NoTx) under real-world conditions. Methods: In a prior analysis of this multicenter, retrospective cohort study, patients with resected melanoma stage III-IV between 06/2018 and 09/2019 were analyzed for adjuvant therapy choice (Lodde et al., Cancers 2021). In this follow-up study, the treatment course of ICI- and TT-treated patients as well as recurrence characteristics, subsequent management and outcomes also including NoTx patients were examined. Results: 814 patients were included (72 stage IIIA, 266 IIIB, 383 IIIC, 24 IIID, 69 IV; 309 BRAF mut); 533 patients received ICI (66%), 114 TT (14%, 36.9% of all BRAF mutated patients), 167 patients had opted for NoTx (21%). Median treatment duration was 10.2 and 11.7 months for ICI and TT, respectively. ICI was discontinued prematurely in 51% (273/533) and TT in 44% (50/114) of patients. The main reason for discontinuation was progressive disease (PD) in ICI patients (58%, 158/273) and adverse events in TT patients (60%, 33/50). At a median follow-up (FU) of 24.6 months for ICI, 25.3 months for TT, and 21.8 months for NoTx, 48% of ICI (255/533), 35% of TT (40/114), and 45% of NoTx (75/167) patients had developed a recurrence mostly at distant sites (ICI 62%, TT 63%, NoTx 64%). In patients with recurrence, median time from start of adjuvant treatment to 1st recurrence was 6.1 months in ICI and 17.6 months in TT. Median RFS was 32.0 months for ICI (95% CI 25.7-38.3), not reached for TT, and 22.3 months for NoTx (95% CI 15.2-29.4). Among BRAF mut patients with stage III, risk of recurrence was higher for ICI than TT (hazard ratio adjusted for age, sex and tumor stage, 2.31; 95% CI 1.56-3.43). Subsequent systemic treatment for the 1st recurrence was given in 76% (192/253) of ICI, 83% (33/40) of TT, and 53% (40/75) of NoTx patients. Among patients who received the 1st subsequent systemic treatment for metastatic disease, PD was the best response in 67% (82/123) for ICI, 55% (11/20) for TT, and 50% (16/32) for NoTX. Conclusions: After 2 years of FU, recurrences were mostly at distant sites in all groups. ICI had higher discontinuation rates and more and earlier recurrences than TT. BRAF mut melanoma patients treated with ICI had a significantly higher risk of relapse than TT-treated patients. Response to subsequent systemic treatment was low for both ICI and TT.

New and Emerging Targeted Therapies for Advanced Breast Cancer.

In the United States, breast cancer is among the most frequently diagnosed cancers in women. Breast cancer is classified into four major subtypes: human epidermal growth factor receptor 2 (HER2), Luminal-A, Luminal-B, and Basal-like or triple-negative, based on histopathological criteria including the expression of hormone receptors (estrogen receptor and/or progesterone receptor) and/or HER2. Primary breast cancer treatments can include surgery, radiation therapy, systemic chemotherapy, endocrine therapy, and/or targeted therapy. Endocrine therapy has been shown to be effective in hormone receptor-positive breast cancers and is a common choice for adjuvant therapy. However, due to the aggressive nature of triple-negative breast cancer, targeted therapy is becoming a noteworthy area of research in the search for non-endocrine-targets in breast cancer. In addition to HER2-targeted therapy, other emerging therapies include immunotherapy and targeted therapy against critical checkpoints and/or pathways in cell growth. This review summarizes novel targeted breast cancer treatments and explores the possible implications of combination therapy.

Chronological age or biological age: What drives the choice of adjuvant treatment in elderly breast cancer patients?

Ma and colleagues reported in their study on 12,004 elderly patients published on Breast J. 2020, that adjuvant chemotherapy was not associated with overall survival. Given the toxicities associated with systemic treatments, caution recommendation or omission of chemotherapy may be considered in elderly patient selection especially when comorbidities are present. We agree with authors final conclusions but we want to highlight that to define the adjuvant therapy in BC elderly patients several factors need to be taken into account. One of the main issues is the lack of universal and unique guidelines to define elderly patients. In clinical practice it can be very difficult to estimate the benefit/risk ratio in elderly patients because chemotherapy-induced toxicity is worse than in younger individuals. For these reasons, beyond comorbidities, the choice of adjuvant therapy for elderly patients must also be based both on chronological and biological age. Moreover, the multidisciplinary team for the elderly patient evaluation should include both the geriatrician and the molecular biologist.

Clinician's commentary: Atypical peritoneal cytology in ovarian and endometrial cancers.

Peritoneal cytology results play an important role in staging, prognostication, and treatment recommendations in early-stage ovarian cancer. In endometrial cancer, while no longer part of staging criteria, peritoneal cytology results can influence patient-provider shared-decision making regarding adjuvant therapy choices after definitive surgery. We explore two cases demonstrating the impact uncertain cytology can have on patients and providers in these two gynecologic cancers.

Risk Stratification of Early-Stage Cervical Cancer with Intermediate-Risk Factors: Model Development and Validation Based on Machine Learning Algorithm.

BackgroundAdjuvant therapy for patients with cervical cancer (CC) with intermediate‐risk factors remains controversial. The objectives of the present study are to assess the prognoses of patients with early‐stage CC with pathological intermediate‐risk factors and to provide a reference for adjuvant therapy choice.Materials and MethodsThis retrospective study included 481 patients with stage IB–IIA CC. Cox proportional hazards regression analysis, machine learning (ML) algorithms, Kaplan‐Meier analysis, and the area under the receiver operating characteristic curve (AUC) were used to develop and validate prediction models for disease‐free survival (DFS) and overall survival (OS).ResultsA total of 35 (7.3%) patients experienced recurrence, and 20 (4.2%) patients died. Two prediction models were built for DFS and OS using clinical information, including age, lymphovascular space invasion, stromal invasion, tumor size, and adjuvant treatment. Patients were divided into high‐risk or low‐risk groups according to the risk score cutoff value. The Kaplan‐Meier analysis showed significant differences in DFS (p = .001) and OS (p = .011) between the two risk groups. In the traditional Sedlis criteria groups, there were no significant differences in DFS or OS (p > .05). In the ML‐based validation, the best AUCs of DFS at 2 and 5 years were 0.69/0.69, and the best AUCs of OS at 2 and 5 years were 0.88/0.63.ConclusionTwo prognostic assessment models were successfully established, and risk grouping stratified the prognostic risk of patients with CC with pathological intermediate‐risk factors. Evaluation of long‐term survival will be needed to corroborate these findings.Implications for PracticeThe Sedlis criteria are intermediate‐risk factors used to guide postoperative adjuvant treatment in patients with cervical cancer. However, for patients meeting the Sedlis criteria, the choice of adjuvant therapy remains controversial. This study developed two prognostic models based on pathological intermediate‐risk factors. According to the risk score obtained by the prediction model, patients can be further divided into groups with high or low risk of recurrence and death. The prognostic models developed in this study can be used in clinical practice to stratify prognostic risk and provide more individualized adjuvant therapy choices to patients with early‐stage cervical cancer.

P14.32 Patterns of invasion in Glioblastoma have unique radiological features, varied response to radiotherapy and long term outcomes

Abstract BACKGROUND To assess the correlation of the three patterns of invasion of Glioblastoma (GB) with the respective MRI features, response to radiotherapy and disease free survival MATERIAL AND METHODS Histopathology of 62 patients with Glioblastoma who had undergone maximal safe resection (MSR)/ stereotactic biopsy (STB) &amp; referred for adjuvant therapy was reviewed to assess the pattern of invasion. Three patterns were observed- single cell infiltration (pattern 1), perineuronal satellitosis (pattern 2) and vessel cooption (or perivascular spread, pattern 3), majority also had diffuse infiltration pattern in the background. The pre and post operative MRI scans were utilized for RT planning of 3DCRT/ IMRT/ VMAT, the modality decided by the treating oncologist. RT volumes were as per ESTRO-ACROP guidelines. Duration of radiotherapy- the Stupp regimen or a short course of hypofractionated radiotherapy (HFRT) (35Gy/10Fr- planned gap- completion of total dose) was based on the extent of resection (EOR) and KPS at the time of RT. Correlation of the pattern of invasion, MRI characteristics of each on the response to radiotherapy as assessed by RANO criteria and survival was analysed with the help of SPSS V21. RESULTS MRI findings after stratification of 62 patients, median age 43 years(18–70), M:F::42:20) into type 1:17, type 2:21 and type 3:24- patterns of invasion, were cortical tumours (subtle enhancement) close to SVZ, solid (+/- cystic) lesion in the eloquent cortex or large mass effect crossing the barriers respectively. OS of entire cohort at 1 year was 75%, with significant differences among groups (82% vs. 85% vs. 50%). Among pattern 1, those patients with IDH mutant (20%) &amp; mean dose to C/L SVZ of 30Gy or more had longer DFS at 1 year (89% Vs. 38% &amp; 85% vs. 0%, p&amp;lt;0.05). In pattern 2, EOR (gross total or near total resection Vs. only STB) showed a better DFS at 1 year (90% vs. 40%, p=0.095). In patients with pattern 3, 40% had post op KPS of &amp;lt;80 and 20% of them underwent HFRT who showed higher CR/PR rates compared to the conventional RT. HFRT in low KPS with m-MGMT showed higher local control at 6 months (100% Vs. 66%, p= 0.02). CONCLUSION Glioblastoma has three patterns of invasion with unique MRI features and aggressiveness for each. Identification of this may guide choice of adjuvant therapy, patterns of failure and therapy resistance

Abstract #1002357: A Rare Case of Acute Liver Failure following the use of Mitotane for Treatment of Adrenal Cortical Carcinoma

Adrenal Cortical Carcinoma (ACC) is a rare tumor (annual incidence 0.7–2.0 cases/million). Surgery is first line treatment, with mitotane being the choice for adjuvant therapy after surgical resection. Hepatotoxicity from mitotane is usually mild, transient, and associated with transaminitis. Though there have been cases of acute liver injury reported in animals, there are no documented cases of mitotane-induced acute liver failure in humans. We present the first reported case of ACC, associated with acute liver failure due to mitotane use, requiring a liver transplant.